Xuejing Chen

Retinal Capillary Density and Foveal Avascular Zone Area Are Age-Dependent: Quantitative Analysis Using Optical Coherence Tomography Angiography.

Purpose The purpose of this study was to quantify retinal capillary density and the foveal avascular zone (FAZ) area in normal subjects according to age, using optical coherence tomography angiography (OCTA). Methods All eyes in this cross-sectional study underwent OCTA using RTVue XR Avanti with AngioVue. OCTA scans were analyzed and processed, and vessel density and FAZ dimensions were calculated. Results A total of 113 normal eyes from 70 subjects were included (30 males, 40 females; mean 48 ± 20 years of age). The mean vessel density and FAZ dimensions were significantly smaller in the superficial retinal capillary plexus (SCP) than in the deep retinal capillary plexus (DCP), using quantitative OCTA analysis (all P< 0.0001). With 3 × 3-mm scans, the mean vessel density was 13.431 ± 1.758 mm-1 in the SCP, 18.812 ± 1.796 mm-1 in the DCP, and 5.913 ± 1.308 mm-1 and 10.447 ± 1.262 mm-1 with 6 × 6-mm scans in the SCP and DCP, respectively. Mean FAZ areas were 0.289 ± 0.108 mm2 at the SCP and 0.614 ± 0.200 mm2 at the DCP. Age was a predictor of SCP and DCP vessel density and FAZ area in the SCP. Vessel density decreased 0.0393 mm-1 (0.26%) per year in the SCP and 0.0574 mm-1 (0.27%) per year in the DCP. FAZ areas increased 0.0014 mm2 (0.63%) and 0.0011 mm2 (0.20%) per year in the SCP and DCP, respectively. Conclusions SCP and DCP vessel density decreased with increasing age, while FAZ area increased with age. Normal age-matched measurements provide important standardized values that may facilitate management of retinal vascular disorders.

Spectrum of Retinal Vascular Diseases Associated With Paracentral Acute Middle Maculopathy.

PURPOSE To evaluate the spectrum of retinal diseases that can demonstrate paracentral acute middle maculopathy and isolated ischemia of the intermediate and deep capillary plexus. DESIGN Retrospective, multicenter, observational case series. METHODS This is a retrospective case series review of 9 patients (10 eyes) from 5 centers with paracentral acute middle maculopathy lesions and previously unreported retinal vascular etiologies. Case presentations and multimodal imaging, including color photographs, near-infrared reflectance, fluorescein angiography, spectral-domain optical coherence tomography (SD OCT), and orbital color Doppler imaging, are described. Baseline and follow-up findings are correlated with clinical presentation, demographics, and systemic associations. RESULTS Five men and 4 women, aged 27-66 years, were included. Isolated band-like hyperreflective lesions in the middle retinal layers, otherwise known as paracentral acute middle maculopathy, were observed in all patients at baseline presentation. Follow-up SD OCT analysis of these paracentral acute middle maculopathy lesions demonstrated subsequent thinning of the inner nuclear layer. Novel retinal vascular associations leading to retinal vasculopathy and paracentral acute middle maculopathy include eye compression injury causing global ocular ischemia, sickle cell crisis, Purtschers retinopathy, inflammatory occlusive retinal vasculitis, post-H1N1 vaccine, hypertensive retinopathy, migraine disorder, and post-upper respiratory infection. CONCLUSION Paracentral acute middle maculopathy lesions may develop in a wide spectrum of retinal vascular diseases. They are best identified with SD OCT analysis and may represent ischemia of the intermediate and deep capillary plexus. These lesions typically result in permanent thinning of the inner nuclear layer and are critical to identify in order to determine the cause of unexplained vision loss.

Optical coherence tomography angiography of type 3 neovascularisation in age-related macular degeneration after antiangiogenic therapy

Background/aims To assess the microvascular response of type 3 neovascularisation secondary to age-related macular degeneration (AMD) after antivascular endothelial growth factor (anti-VEGF) therapy using optical coherence tomography angiography (OCTA). Methods Consecutive patients diagnosed with AMD and type 3 neovascularisation based on clinical examination, structural optical coherence tomography and fluorescein angiography when available were retrospectively evaluated. En face OCTA imaging (3×3 mm scans) with quantitative microvascular analysis was performed at baseline and after a single anti-VEGF intravitreal injection. Results 17 eyes of 14 patients underwent OCTA before and after anti-VEGF treatment. OCTA demonstrated significant regression of small calibre type 3 neovascular tufts in all eyes. Median lesion area was 0.061 mm2 (range 0.003–0.198 mm2) at baseline and 0.009 mm2 (range 0–0.085 mm2, p=0.0003) at follow-up. Cystoid macular oedema and/or subretinal fluid resolved in all cases after treatment. The type 3 lesions became undetectable with OCTA post-treatment in 5 of the 17 eyes. However, in 11 eyes, large feeder vessels were identified and remained unchanged after treatment. Conclusions The microvascular morphology of type 3 neovascularisation secondary to AMD was assessed at baseline and follow-up and showed significant regression in response to anti-VEGF therapy by OCTA. Quantitative OCTA analysis was also performed and confirmed remarkable regression in response to a single intravitreal anti-VEGF injection.

CORRELATION OF MULTIMODAL IMAGING IN SICKLE CELL RETINOPATHY

Purpose: To correlate macular findings on spectral domain optical coherence tomography (SDOCT) and optical coherence tomography angiography (OCTA) with quantitative ischemic index calculations on ultra-wide-field fluorescein angiography (UWFFA) in patients with sickle cell retinopathy. Methods: In this retrospective case series, SDOCT, OCTA, and UWFFA images of patients with sickle cell retinopathy were evaluated. Eyes were staged based on the Goldberg classification of proliferative sickle cell retinopathy. Focal areas of macular thinning were assessed on SDOCT, macular vessel density was derived from OCTA, and peripheral ischemic index was calculated from UWFFA. Results: Eighteen eyes of 10 patients were included. Mean age was 36.8 ± 16.8 years, and 6 patients (11 eyes) were SS, 3 patients (5 eyes) were SC, and 1 patient (2 eyes) was S&bgr; thalassemia in hemoglobin electrophoresis. Abnormal macular findings included inner retinal atrophy in 11 eyes (61%) on SDOCT, vascular remodeling and nonperfusion in the superficial and deep retinal capillary plexus in 12 eyes (67%) on OCTA, and macular microvascular abnormalities in 9 eyes (50%) on UWFFA. Sickle cell retinopathy Stage I was identified in 4 eyes (22.2%), Stage II in 8 eyes (44.4%), and Stage III in 6 eyes (33.3%). Mean ischemic index was 14.1 ± 9.1%. Ischemic index was significantly correlated with hemoglobinopathy subtype (23.7 ± 9.8%, 9.3 ± 5.4%, and 16.3 ± 3.2%, for SC, SS, and S&bgr; thalassemia disease, respectively), stage of sickle cell retinopathy (22.5 ± 9.2%, 12.5 ± 4.9%, and 4.5 ± 0.73% for Stages III, II, and I, respectively), and presence of retinal thinning on SDOCT (17.4 ± 9.7% vs. 8.8 ± 5.1%, respectively). Conclusion: Multimodal imaging can provide a more complete description of the microvascular and structural alterations associated with sickle retinopathy. The correlation between the severity of peripheral nonperfusion and stage and subtype of retinopathy suggests that UWF imaging may be a useful tool in the evaluation of these patients.PURPOSE To correlate macular findings on spectral domain optical coherence tomography (SDOCT) and optical coherence tomography angiography (OCTA) with quantitative ischemic index calculations on ultra-wide-field fluorescein angiography (UWFFA) in patients with sickle cell retinopathy. METHODS In this retrospective case series, SDOCT, OCTA, and UWFFA images of patients with sickle cell retinopathy were evaluated. Eyes were staged based on the Goldberg classification of proliferative sickle cell retinopathy. Focal areas of macular thinning were assessed on SDOCT, macular vessel density was derived from OCTA, and peripheral ischemic index was calculated from UWFFA. RESULTS Eighteen eyes of 10 patients were included. Mean age was 36.8 ± 16.8 years, and 6 patients (11 eyes) were SS, 3 patients (5 eyes) were SC, and 1 patient (2 eyes) was Sβ thalassemia in hemoglobin electrophoresis. Abnormal macular findings included inner retinal atrophy in 11 eyes (61%) on SDOCT, vascular remodeling and nonperfusion in the superficial and deep retinal capillary plexus in 12 eyes (67%) on OCTA, and macular microvascular abnormalities in 9 eyes (50%) on UWFFA. Sickle cell retinopathy Stage I was identified in 4 eyes (22.2%), Stage II in 8 eyes (44.4%), and Stage III in 6 eyes (33.3%). Mean ischemic index was 14.1 ± 9.1%. Ischemic index was significantly correlated with hemoglobinopathy subtype (23.7 ± 9.8%, 9.3 ± 5.4%, and 16.3 ± 3.2%, for SC, SS, and Sβ thalassemia disease, respectively), stage of sickle cell retinopathy (22.5 ± 9.2%, 12.5 ± 4.9%, and 4.5 ± 0.73% for Stages III, II, and I, respectively), and presence of retinal thinning on SDOCT (17.4 ± 9.7% vs. 8.8 ± 5.1%, respectively). CONCLUSION Multimodal imaging can provide a more complete description of the microvascular and structural alterations associated with sickle retinopathy. The correlation between the severity of peripheral nonperfusion and stage and subtype of retinopathy suggests that UWF imaging may be a useful tool in the evaluation of these patients.

AN UPDATED STAGING SYSTEM OF TYPE 3 NEOVASCULARIZATION USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

Purpose: To comprehensively investigate spectral domain optical coherence tomography features associated with Type 3 neovascularization and determine the prevalence of each feature and to develop an updated staging system for Type 3 neovascularization based on spectral domain optical coherence tomography findings. Methods: The authors retrospectively analyzed 34 eyes with new-onset Type 3 neovascularization. Spectral domain optical coherence tomography images at onset of Type 3 neovascularization, immediately after the first injection, and at the final quiescent visit were analyzed for the presence of specific optical coherence tomography features. In addition, when available, optical coherence tomography images from the visit before onset were studied. Results: Among 18 eyes with preonset optical coherence tomography, 77.8% had preexisting intraretinal hyperreflective foci (precursor lesion). In the same group of eyes, 44.4% and 27.8% exhibited outer plexiform layer disruption and outer plexiform layer downward deflection, respectively. At the onset of detectable Type 3 neovascularization, all 34 eyes demonstrated a hyperreflective focus with cystoid macular edema and 85.3% exhibited disruption of the retinal pigment epithelium. Serous pigment epithelial detachment and subretinal fluid were present in 67.6% and 23.5% of eyes at onset, respectively. The rate of cystoid macular edema decreased from 100% to 17.6% after a single injection. At the final quiescent visit, focal atrophy at the site of Type 3 lesions, as evidenced by outer retinal and retinal pigment epithelium disruption developed in 88.2% and 52.9% of eyes, respectively. Conclusion: An updated staging system of Type 3 lesions was developed based on spectral domain optical coherence tomography findings. A precursor stage consists of a punctate hyperreflective focus in the outer retina. The subtle detection of associated outer plexiform layer disruption and downward deflection may indicate that this precursor lesion is more likely to progress to an active Type 3 neovascular lesion. Stage 1 consists of a larger intraretinal hyperreflective lesion associated with cystoid macular edema but without outer retinal disruption. Stage 2 is notable for outer retinal disruption that occurs with retinal pigment epithelium disruption in most of the cases. Stage 3 is defined by an intraretinal hyperreflective lesion that extends through the retinal pigment epithelium to vascularize a drusenoid pigment epithelial detachment creating a serous component of the pigment epithelial detachment.

TYPE 1 VERSUS TYPE 3 NEOVASCULARIZATION IN PIGMENT EPITHELIAL DETACHMENTS ASSOCIATED WITH AGE-RELATED MACULAR DEGENERATION AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY: A Prospective Study.

Purpose: To evaluate the response to aflibercept therapy for Type 1 and Type 3 neovascularization in pigment epithelial detachments associated with treatment-naive, neovascular age-related macular degeneration. Methods: In this multicentered, prospective study, eligible eyes underwent an intravitreal aflibercept injection protocol for 12 months. Visual acuity and morphologic features of the pigment epithelial detachments were compared at baseline and follow-up intervals between eyes with Type 1 versus Type 3 neovascularization. Results: Thirty-six eyes were analyzed. At 12 months, Type 1 lesions showed a 4.5 ± 23 Early Treatment of Diabetic Retinopathy Study letter improvement (P = 0.1665) versus a 14 ± 11 (P = 0.0072) letter improvement with Type 3 lesions. Both Type 1 and 3 eyes showed a significant decrease in pigment epithelial detachment size, subretinal fluid, and subretinal hyperreflective material; however, Type 3 eyes had a greater reduction in pigment epithelial detachment size and subretinal hyperreflective material, as well as a reduction in central retinal thickness. Type 1 eyes required an average of 1.636 (range, 1–4) injections to resolve fluid, which was greater than Type 3 eyes, which required an average of 1.143 (range, 1–2) injections (P = 0.0251). Conclusion: Intravitreal aflibercept injections were efficacious for pigment epithelial detachments, but baseline and follow-up anatomical and functional outcomes differed in Type 1 versus Type 3 neovascularization. The better response of Type 3 eyes with fewer injections suggests that differentiation of the neovascularization subtype at the initial diagnosis may allow for a more tailored, optimal therapy.

DOUBLE RETINAL PIGMENT EPITHELIUM TEARS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

Purpose: To describe the occurrence and treatment outcomes of double retinal pigment epithelium (RPE) tears in neovascular age-related macular degeneration and to elucidate the mechanism of tear development by means of multimodal imaging analysis. Methods: Fundus autofluorescence, spectral-domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography were retrospectively studied before and after the occurrence of first and second RPE tears and at the final visit. Results: Twelve eyes of 10 patients that developed double RPE tears, either simultaneously (6 eyes) or at variable intervals after repeated intravitreal anti–vascular endothelial growth factor administration (6 eyes), were included. First RPE tears developed after a mean of 4.5 ± 2.7 anti–vascular endothelial growth factor injections; second RPE tears developed after a mean of 7.1 ± 5.2 anti–vascular endothelial growth factor injections. Mean best-corrected visual acuity was 20/63 at baseline evaluation, 20/76 after occurrence of first tear, 20/90 after occurrence of second tear, and 20/95 at final visit (P > 0.05 for all). Multimodal imaging revealed in all cases a Type 1 neovascular lesion adherent to the posterior surface of the RPE and spanning a significant portion of the pigment epithelium detachment with variable orientation; after development of double tears, the RPE seemed retracted on both borders of the neovascular network. Conclusion: Double RPE tears may occur on opposite sides of a vascularized pigment epithelium detachment, in eyes with neovascular age-related macular degeneration after anti–vascular endothelial growth factor therapy, because of neovascular contraction of a Type 1 neovascular complex, adherent to the posterior surface of the RPE and spanning a significant portion of the pigment epithelium detachment area.

EN FACE OPTICAL COHERENCE TOMOGRAPHY OF MACULAR MICROCYSTS DUE TO OPTIC NEUROPATHY FROM NEUROMYELITIS OPTICA.

PURPOSE To describe the multimodal imaging, including en face optical coherence tomography (OCT) and OCT angiography, findings of a case of macular microcysts associated with neuromyelitis optica. METHODS Findings on clinical examination, color fundus photography, fluorescein angiography, fundus autofluorescence, visual fields, and OCT including en face OCT and OCT angiography are presented. RESULTS A 12-year-old African American boy presented with bilateral optic atrophy from neuromyelitis optica. Clinical examination was notable for bilateral optic nerve head pallor. Visual fields of both eyes showed generalized depression. Fluorescein angiography and fundus autofluorescence were unremarkable. Spectral domain OCT B-scan images showed characteristic paracentral, hyporeflective, microcystic lesions in the inner nuclear layer of both eyes, and en face OCT images demonstrated a corresponding pattern of large paracentral cysts radiating peripherally into smaller diffuse cysts. Optical coherence tomographic angiography of the superficial and deep retinal capillary plexuses was unremarkable. CONCLUSION Macular microcysts have been associated with various forms of optic atrophy, including neuromyelitis optica. Spectral domain and en face OCT imaging of the microcysts demonstrated a very characteristic pattern. Normal fluorescein and OCT angiography suggest that nonvascular causes, such as Müller cell degeneration, might contribute to the etiologic mechanism.

Outcomes of intravitreal anti-VEGF therapy in eyes with both neovascular age-related macular degeneration and diabetic retinopathy.

Purpose To investigate the outcomes of intravitreal antivascular endothelial growth factor (VEGF) therapy in eyes with both neovascular age-related macular degeneration (AMD) and diabetic retinopathy (DR). Methods Patients from four high-volume referral centres who presented with neovascular AMD and DR, and received intravitreal anti-VEGF therapy, were included. Data retrieved from medical records and multimodal imaging were analysed. Results Forty-one eyes of 38 patients (21 male, 17 female; mean age 78±8 years) were enrolled. Median follow-up was 28±19 (12–72) months with a mean of 9.2±7.4 intravitreal anti-VEGF injections per eye were administrated. Best-corrected visual acuity (BCVA) was 0.5±0.3 logMAR; it improved significantly at 1 year (0.3±0.3 logMAR; p=0.02) and returned to baseline values at last follow-up visit (0.6±0.4 logMAR; p=0.26). Mean central macular thickness (CMT) significantly decreased from 408±150 μm to 328±104 μm at 1 year (p=0.021) and to 335±127 μm at last follow-up visit (p=0.032). The baseline severity of DR was graded as mild non-proliferative DR (NPDR) in 21 (51%) eyes, moderate NPDR in 14 (34%), severe NPDR in 4 (10%) and inactive proliferative DR in 2 (5%). At last follow-up visit, one eye graded as moderate NPDR improved to mild, one eye graded as severe NPDR improved to mild and one eye graded as severe NPDR was inactivated due to panretinal photocoagulation. Conclusions Outcomes analysis of intravitreal anti-VEGF therapy for eyes with both neovascular AMD and DR showed stabilisation of BCVA and reduction of CMT, along with stable or improved DR stage throughout follow-up.

Parafoveal Retinal Vessel Density Assessment by Optical Coherence Tomography Angiography in Healthy Eyes

BACKGROUND AND OBJECTIVE To assess variability in vessel density (VD) measurements across three optical coherence tomography angiography (OCTA) devices to identify a methodology that offers the least amount of variation in VD, and to assess the effect of averaging of multiple scans on VD variability. PATIENTS AND METHODS Fifteen eyes of eight healthy individuals were imaged consecutively on three OCTA devices. Segmentations at the superficial, deep, and full retinal layers were generated. Repeat scans for each retinal layer were registered and averaged to generate one OCTA image. Two different automated thresholding techniques were used to calculate vessel area density (VAD) from binarized images and vessel skeleton density (VSD) from skeletonized images. Vessel length, a linear measure of the combined lengths of vessels, was calculated. Foveal avascular zone (FAZ) area was measured. RESULTS All three OCTA devices were significantly different (P < .0001). This finding remained after averaging images (P < .0001). VSD was more repeatable within a device but less reproducible across devices. Conversely, VAD demonstrated less repeatability but greater reproducibility. Differences in VSD between devices were systematic and attributable to differences in resolution. Vessel length, unaffected by resolution, demonstrated no significant differences between the devices (P > .107). There was no significant difference in FAZ area across devices (P = .51). After averaging images, VD was significantly different from the single images for each device and plexus (P < .05) but remained within 1% of the value of a single scan. CONCLUSIONS OCTA devices show variability in VD for healthy individuals. With greater repeatability, VSD appeared useful for following a patient on one device. VAD and vessel length seemed ideal for comparing vessel parameters between OCTA devices. After averaging multiple scans, VSD remained within 1% of a single scan, for which clinical significance remains to be determined. Caution is advised when comparing quantitative analyses across OCTA devices. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:S5-S17.].